The aim of the proposed study is to further the mission of the NIMH's Side Effects of Psychiatric Therapeutics Program by (1) developing and testing an acute exercise-based intervention for sexual side effects of selective serotonin reuptake inhibitors (SSRIs) and (2) assessing the psychophysiological effects of different neurotransmitter selectivity profiles of SSRIs on sexual functioning in women. We will use a paradigm to test effects of exercise on women experiencing sexual side effects of SSRIs. Participants will act as their own controls in a three counterbalanced assessments. In the baseline assessment, women will fill out questionnaires for 20 minutes and then watch a 10-minute film while their physiological response is recorded using a photoplethysmograph and electrocardiogram and continuous subjective response is recorded using a mouse-controlled lever. In the "high SNS" assessment, the women will exercise at 70% of their maximum heart rate for 20 minutes, wait 5 minutes, and then watch a different 10-minute film while their physiological and subjective response is recorded. In the "low SNS" assessment, the women will exercise for 20 minutes, wait 15 minutes (to induce the shift from sympathetic nervous system activity to parasympathetic activity), and then watch a 10-minute film while their physiological response is recorded. Psychophysiological measurements of response at baseline will be compared to high and low SNS conditions. To test the differences between different neurotransmitter selectivity profiles, we will recruit equal numbers of women taking sertraline, paroxetine, or citalopram (highly selective for serotonin relative to norephinephrine) and venlafaxine or duloxetine (selective serotonin and norephinephrine reuptake inhibitors, or SNRIs). It is expected that SNS activity will be lowest in women taking paroxetine/sertraline/citalopram and that these women would benefit most from an acute SNS activity intervention. In terms of public health, the proposed study's aim of testing the efficacy of an exercise-based intervention for side effects of SSRIs has the potential not only to develop an inexpensive, easily accessible management system for side effects but also to further our understanding of the underlying biological and psychological mechanisms which give rise to these effects. This knowledge may help doctors advise and treat patients who take these drugs, and may help scientists create new drugs with mitigated side effect profiles. PUBLIC HEALTH RELEVANCE: In terms of public health, the proposed study's aim of testing the efficacy of an exercise-based intervention for side effects of SSRIs has the potential not only to develop an inexpensive, easily accessible management system for side effects but also to further our understanding of the underlying biological and psychological mechanisms which give rise to these effects. This knowledge may help doctors advise and treat patients who take these drugs, and may help scientists create new drugs with mitigated side effect profiles.